Dados do Trabalho

Título

BONE MARROW MONONUCLEAR CELLS TRANSPLANTATION MODULATES BRAIN GLUCOSE METABOLISM AND METABOLIC NETWORK AND REDUCES DEPRESSIVE-LIKE BEHAVIOR IN CHRONIC EPILEPSY

Introdução

Depression is a frequent psychiatric comorbidity in patients with epilepsy. Although the psychosocial aspects of these patients may contribute to a depressive condition associated with epilepsy, studies have suggested that epilepsy and depression are associated with common neuropathogenic mechanisms. Recently, we showed a brain glucose hypometabolism in regions related to epilepsy and depression, and an altered metabolic brain network (MBN) in epileptic rats with depressive-like behavior. Bone marrow mononuclear cells (BMMCs) have been used for epilepsy treatment and have shown beneficial therapeutic effects.

Objetivo

Here, we investigated the effect of BMMCs transplantation on depressive-like behavior, brain glucose metabolism and MBN in epileptic animals.

Método

Epilepsy model was induced by pilocarpine (320 mg/kg, ip). Chronically epileptic rats were intravenously transplanted with 1×107 BMMCs isolated from GFP transgenic rats. Micro–positron emission tomography (microPET) imaging associate with fluorodeoxyglucose (18F-FDG) was used to investigate the brain metabolism and MBN. Forced swim test, sucrose preference test, and eating-related depression test were used to evaluate depressive-like behavior. Seizure occurrence was monitored pre and post-transplantation.

Resultados

Our results showed that the epileptic group presents a brain glucose hypometabolism and a hypersynchronous MBN in relation to the control and BMMC-treated groups, with aberrant connections in brain regions related to both pathologies. Contrastingly, BMMC-treated group reveals increased brain glucose metabolism and a decrease of aberrant connections between specific brain regions. Also, BMMC transplantation reduced seizure frequency and depressive-like behavior in epileptic rats. Thus, the present study suggests a potential effect of BMMCs transplantation for modulation of the interregional connections in the MBN, reducing seizure frequency and depression-like behavior in epileptic animals.

Conclusão

Clinically, the emergence of depression may cause a significant worsening of quality of life in epileptic patients. Within this scenario, our findings are especially important for a better understanding of common mechanisms of depression and epilepsy in order to be able to search for new effective and safe strategies for the treatment and prevention of this condition. Thus, the positive effects we observed suggest that BMMC transplantation could be an option for the management of chronic epilepsy and depression comorbidity.

Palavras-chave

Epilepsy; Depression; Metabolic Brain Network